Neurodegenerative disease risk associated with gene expression in peripheral monocytes across ancestries
Abstract
Abstract It is hypothesised that peripheral immune states responding to regional environmental triggers contribute to central neurodegeneration. Region-specific genetic selection pressures require this hypothesis to be assessed in an ancestry-specific manner. Here, we utilise genome-wide association studies and expression quantitative trait loci from African, East Asian and European ancestries to show that genes causally-implicated in neurodegeneration are preferentially expressed in innate rather than adaptive immune cells. Using colocalisation and Mendelian randomisation analyses, we show that in addition to known colocalising signals in microglia, genetic variants associated with neurodegenerative disease risk also regulate the expression of these genes in peripheral monocytes across ancestries.
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Authors: Aaron Z. Wagen, Regina Hertfelder Reynolds, Jia Nee Foo, Emil Karl Gustavsson, Nicholas William Wood, Sarah A. Gagliano Taliun, Chris Wallace, Cornelis Blauwendraat, Sonia Gandhi, Mina Ryten
Institutions: Université de Montréal, University College London, University of Cambridge, MRC Biostatistics Unit, National Institutes of Health, Nanyang Technological University, National Institute on Aging, National Institute of Neurological Disorders and Stroke, Montreal Heart Institute, The Francis Crick Institute, UCL Queen Square Institute of Neurology, Aligning Science Across Parkinson's